What is the appropriate workup for a patient with amenorrhea (absence of menstruation)?

Workup of Amenorrhea

The appropriate workup for amenorrhea should follow a systematic approach beginning with pregnancy exclusion, followed by evaluation of hormone levels (FSH, LH, TSH, prolactin), and progesterone challenge testing to determine the underlying cause. 1, 2

Initial Assessment

History

• Menstrual history: age of menarche, regularity of cycles, duration of amenorrhea
• Weight changes or disordered eating patterns
• Exercise habits (especially high-intensity training)
• Stress levels and psychological stressors
• Medication use (including hormonal contraceptives)
• Symptoms of hyperandrogenism (hirsutism, acne)
• Galactorrhea
• Headaches or visual changes (suggesting pituitary pathology)
• Hot flashes or vaginal dryness (suggesting hypoestrogenism)
• Family history of menstrual disorders or early menopause

Physical Examination

• Height, weight, BMI calculation
• Vital signs
• Thyroid examination
• Breast examination for galactorrhea
• Signs of hyperandrogenism (hirsutism, acne)
• Pelvic examination to assess outflow tract patency and development
• Pubertal development assessment (Tanner staging)

Laboratory and Diagnostic Testing Algorithm

1. Pregnancy test - Must be performed first in all cases of amenorrhea 3

2. Initial hormone panel:

   • FSH (follicle-stimulating hormone)
   • LH (luteinizing hormone)
   • Prolactin
   • TSH (thyroid-stimulating hormone) 1, 2

3. Progesterone challenge test - Administer medroxyprogesterone acetate 10mg daily for 5-10 days

   • Positive response (withdrawal bleeding): indicates adequate estrogen and patent outflow tract
   • Negative response: indicates hypoestrogenism or outflow tract abnormality 4

4. Based on initial results, consider:

   • Elevated prolactin: Brain MRI to evaluate for pituitary adenoma 1
   • Elevated FSH/LH: Karyotype analysis to evaluate for primary ovarian insufficiency 2
   • Normal/low FSH/LH with negative progesterone challenge: Estrogen-progesterone challenge test
   • Signs of hyperandrogenism: Testosterone, DHEAS, 17-hydroxyprogesterone 2
   • Suspected outflow tract abnormality: Pelvic ultrasound or MRI 1

Specific Diagnostic Pathways

Primary Amenorrhea (no menses by age 15 or 3 years post-thelarche)

• If no sexual development: Karyotype analysis, FSH/LH levels
• If normal pubertal development with uterus: Evaluate for outflow tract obstruction (transverse vaginal septum, imperforate hymen)
• If abnormal uterine development: Evaluate for müllerian agenesis with karyotype analysis 5

Secondary Amenorrhea (cessation of previously established menses)

Based on hormone results:

1. Elevated FSH/LH: Primary ovarian insufficiency

   • Karyotype analysis in women <30 years
   • Consider autoimmune screening
   • Bone mineral density testing 1

2. Normal/Low FSH/LH with negative progesterone challenge: Hypothalamic amenorrhea

   • Evaluate for energy deficiency, stress, excessive exercise
   • Consider brain MRI if other pituitary hormone abnormalities present
   • Bone mineral density testing if duration >6 months 1

3. Normal FSH/LH with positive progesterone challenge: PCOS or other androgen excess disorders

   • Check androgen levels (testosterone, DHEAS)
   • Metabolic screening (glucose tolerance, lipid panel)
   • Pelvic ultrasound 2

4. Elevated prolactin:

   • Brain MRI to evaluate for pituitary adenoma
   • Review medications that can cause hyperprolactinemia 1

5. Abnormal TSH:

   • Complete thyroid function panel
   • Treat underlying thyroid disorder 2

Common Pitfalls and Caveats

• Don't assume amenorrhea with normal BMI excludes energy deficiency - functional hypothalamic amenorrhea can occur in normal-weight women 1
• Don't assume infertility in women with primary ovarian insufficiency - they may have unpredictable ovarian function 2
• Don't miss the diagnosis of female athlete triad/RED-S (Relative Energy Deficiency in Sport) in athletic women 1
• Don't forget to assess bone mineral density in women with prolonged hypoestrogenic amenorrhea (>6 months) 1
• Remember that hormonal contraceptives can mask underlying amenorrhea - obtain an accurate history of menstrual patterns prior to contraceptive use 1

By following this systematic approach, the underlying cause of amenorrhea can be identified in the majority of cases, allowing for appropriate management and prevention of long-term health consequences.